(1) Field of the Invention
The invention is generally related to methods of using pharmaceutical tetrahydroisoquinoline compounds for learning and/or memory enhancement, and for treatment of dementia, cocaine dependence, depression, antiappetite, anxiety, or attention deficit disorder with hyperactivity (ADHD).
(2) Background Information
Phenylalkylamines represent a common structural unit found in many therapeutic agents as well as in certain drugs of abuse. For example, depending upon the presence and location of certain substituent groups, phenylalkylamines might possess central stimulant, hallucinogenic, or designer drug-like activities. Structure A below is the phenylalkylamine central stimulant amphetamine (1-phenyl-2-aminopropane), structure B shows two representative phenylalkyl-amine hallucinogens (viz., 1-2,5-dimethoxy-4-X)-phenyl! -2-aminopropane which is DOM where X=methyl and DOB where X=bromo), structure C shows the phenylalkylamine designer drug 1-(3,4-methylene dioxy)phenyl!-2-(N-methyl)amino!-propane (MDMA or "XTC"), and structure D shows the structurally related agent 1-(3,4-methylenedioxy)phenyl!-2-aminopropane (i.e., MDA) that possesses all three properties of compounds A, B and C. ##STR1##
Studies of certain 1,2,3,4-tetrahydroisoquinolines and certain related analogs thereof, which might be considered as structurally restricted derivatives of A-D, for central stimulant and hallucinogenic effects associated with known phenylalkylamine hallucinogens, e.g., MDMA, or MDA, from a drug abuse and non-therapeutic perspective, have been previously reported. Malmusi, L. et al., Med. Chem. Res., 1996, 6, 400-411; Malmusi, L. et al., Med. Chem. Res., 1996, 6, 412-426; Nakagawa et al., Biol. Pharm. Bull. 1993, 16, 579-582.
As other background information, U.S. Pat. No. 4,908,361 teaches tetrahydroisoquino 2,1-c!1,3!benzodiazepines used for enhancing memory in a mammal. U.S. Pat. No. 5,519,034 teaches certain tetrahydroisoquinoline compounds for use as analgesics, and in the treatment of psychoses, Parkinson's disease, Lesch-Nyan syndrome, attention deficit disorder or cognitive impairment or in the relief of drug dependence or tardive dyskinesia. U.S. Pat. No. 5,118,690 teaches pharmaceutical tetrahydro-isoquinolines for treating pain and/or CNS disorders (e.g., anxiety, epilepsy, muscle spasms, sleep disorders, dyskinesia, depression and/or psychoses) characterized in that the method uses a compound which acts selectively as an antagonist of gamma aminobutyric acid (GABA) at GABA autoreceptors relative to GABA.sub.A receptors. U.S. Pat. No. 5,187,165 teaches various derivatives of esorline and related compounds useful for enhancing cholinergic function, as antidepressants and as analgesic agents. U.S. Pat. No. 4,696,913 teaches peptides which are active on the central nervous system and have an action on the cholinergic system. U.S. Pat. No. 4,622,329 teaches 1-cyclohexyl-3-4-dihydroisoquinoline derivatives which are pharmaceutically active, and in particular show antispasm, analgesic, gastric acid secretion inhibiting, sedative and hypnotic activity and effectively reduce the alcoholic narcosis time.